<br>Janus-ROS 治疗系统通过声表观遗传调节促进感染性骨再生,Advanced Materials

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Janus-ROS 治疗系统通过声表观遗传调节促进感染性骨再生
Advanced Materials ( IF 27.4 ) Pub Date : 2023-10-19 , DOI: 10.1002/adma.202307846
Liang Ma ₁ , Yu Cheng ₂ , Xiaobo Feng ₁ , Xiaoguang Zhang ₁ , Jie Lei ₁ , Hongchuan Wang ₁ , Yan Xu ₁ , Bide Tong ₁ , Dingchao Zhu ₁ , Di Wu ₁ , Xingyu Zhou ₁ , Huaizhen Liang ₁ , Kangcheng Zhao ₁ , Kun Wang ₁ , Lei Tan ₁ , Yanli Zhao ₂ , Cao Yang ₁

Affiliation

感染性骨疾病非常需要消除细菌感染并同时促进成骨分化。大量的活性氧（ROS）会损害细胞，而低浓度的活性氧作为分子信号可以调节细胞的命运。在这项研究中，开发了 Janus-ROS 愈合系统，用于感染性骨再生。制备了阿仑膦酸盐（ALN）介导的缺陷金属有机骨架（MOF）声敏剂，在差异超声照射下可有效清除耐甲氧西林金黄色葡萄球菌（MRSA）感染并促进成骨分化。在锆-磷酸盐配位的情况下，具有适当缺陷的ALN介导的卟啉基MOF（HN25）具有良好的声动力抗菌效率（98.97％，15分钟）和骨靶向能力。值得注意的是，在低功率超声照射下，HN25可以增加骨化相关基因和FOXO1的染色质可及性，从而通过低ROS浓度促进骨修复。椎旁感染、感染性骨折、骨髓炎动物模型表明，HN25通过快速消除MRSA、抑制破骨细胞活性、促进骨再生，成功实现了多种感染性骨组织的靶向强效修复。结果表明，利用药物介导的缺陷工程可以构建高催化效率和生物活性的MOF。 Janus-ROS 治疗也是一种有前途的感染性组织再生治疗模式。

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A Janus-ROS Healing System Promoting Infectious Bone Regeneration via Sono-Epigenetic Modulation

Elimination of bacterial infections and simultaneously promoting osteogenic differentiation are highly required for infectious bone diseases. Massive reactive oxygen species (ROS) can damage cells, while low ROS concentrations as a molecular signal can regulate cellular fate. In this study, a Janus-ROS healing system is developed for infectious bone regeneration. An alendronate (ALN)-mediated defective metal–organic framework (MOF) sonosensitizer is prepared, which can effectively clear Methicillin-resistant Staphylococcus aureus (MRSA) infections and promote osteogenic differentiation under differential ultrasonic irradiation. In the presence of zirconium–phosphate coordination, the ALN-mediated porphyrin-based MOF (HN25) with a proper defect has great sonodynamic antibacterial efficiency (98.97%, 15 min) and bone-targeting ability. Notably, under low-power ultrasound irradiation, HN25 can increase the chromatin accessibility of ossification-related genes and FOXO1 to promote bone repair through low ROS concentrations. Animal models of paravertebral infection, fracture with infection, and osteomyelitis demonstrate that HN25 successfully realizes the targeted and potent repair of various infectious bone tissues through rapid MRSA elimination, inhibiting osteoclast activity and promoting bone regeneration. The results show that high catalytic efficiency and bioactive MOF can be constructed using pharmaceutical-mediated defect engineering. The Janus-ROS treatment is also a promising therapeutic mode for infectious tissue regeneration.

更新日期：2023-10-19

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